当前位置： SCI文献检索 > BIOCHEMICAL PHARMACOLOGY期刊下所有文献 > Novel orally available salvinorin A analog PR-38 protects against experimental colitis and reduces abdominal pain in mice by interaction with opioid and cannabinoid receptors.

Novel orally available salvinorin A analog PR-38 protects against experimental colitis and reduces abdominal pain in mice by interaction with opioid and cannabinoid receptors.

Abstract：

BACKGROUND:Salvinorin A (SA) is a potent anti-inflammatory diterpene isolated from the Mexican plant S. divinorum. Recently we showed that the novel SA analog, PR-38 has an inhibitory effect on mouse gastrointestinal (GI) motility mediated by opioid and cannabinoid (CB) receptors. The aim of the study was to characterize possible anti-inflammatory and antinociceptive action of PR-38 in the mouse GI tract. METHODS:Macro- and microscopic colonic damage scores and myeloperoxidase activity were determined after intraperitoneal (i.p.), intracolonic (i.c.), and per os (p.o.) administration of PR-38 in the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis in mice. Additionally, MOP, KOP and CB1 protein expression was determined using Western blot analysis of mouse colon samples. The antinociceptive effect of PR-38 was examined based on the number of behavioral responses to i.c. instillation of mustard oil (MO). RESULTS:The i.p. (10 mg/kg, twice daily), i.c. (10 mg/kg, twice daily) and p.o. (20 mg/kg, once daily) administration of PR-38 significantly attenuated TNBS- and DSS-induced colitis in mice. The effect of PR-38 was partially blocked by the KOP antagonist nor-binaltorphimine and CB1 antagonist AM 251. Western blot analysis showed a significant increase of MOP, KOP and CB1 receptor expression during colonic inflammation, which was reversed to the control levels by the administration of PR-38. PR-38 significantly decreased the number of pain responses after i.c. instillation of MO in the TNBS-treated mice. CONCLUSIONS:Our results suggest that PR-38 has the potential to become a valuable anti-inflammatory and analgesic therapeutic for the treatment of GI inflammation.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Sałaga M,Polepally PR,Zakrzewski PK,Cygankiewicz A,Sobczak M,Kordek R,Zjawiony JK,Krajewska WM,Fichna J

doi

10.1016/j.bcp.2014.09.018

subject

Has Abstract

pub_date

2014-12-15 00:00:00

pages

618-26

issue

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(14)00562-0

journal_volume

pub_type

杂志文章

在线工具

Novel orally available salvinorin A analog PR-38 protects against experimental colitis and reduces abdominal pain in mice by interaction with opioid and cannabinoid receptors.